Sakarcan A, Aricheta R, Baum M
Department of Pediatrics and Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235-9063.
Pediatr Res. 1992 Dec;32(6):710-3. doi: 10.1203/00006450-199212000-00018.
The present study examined proximal tubular respiration in control proximal tubules and proximal tubules loaded with cystine using 2 mmol/L cystine dimethyl ester. Basal oxygen consumption was significantly less in cystine-loaded tubules (20.6 +/- 0.5 versus 12.1 +/- 0.6 nmol O2.min-1.mg protein-1, p < 0.001). In the presence of 10(-4) mol/L ouabain, an inhibitor of the NaK ATPase, oxygen consumption was 10.2 +/- 0.7 nmol O2.min-1.mg protein-1 in control tubules and 11.4 +/- 1.0 nmol O2.min-1.mg protein-1 in cystine-loaded tubules. Thus, proximal tubular intracellular cystine loading specifically inhibits oxygen metabolism directed toward transport. Compared with control proximal tubules, cystine-loaded proximal tubules also had a lower rate of O2 consumption when the cells were permeabilized to sodium with nystatin and when mitochondrial respiration was uncoupled. Glycine, an amino acid that is cytoprotective to hypoxic proximal tubule injury, ameliorated the respiratory dysfunction observed in cystine-loaded tubules.
本研究使用2 mmol/L胱氨酸二甲酯，检测了对照近端小管和装载胱氨酸的近端小管中的近端小管呼吸。装载胱氨酸的小管中基础氧消耗显著降低（20.6±0.5对12.1±0.6 nmol O2·min-1·mg蛋白-1，p<0.001）。在存在10(-4) mol/L哇巴因（一种钠钾ATP酶抑制剂）的情况下，对照小管中的氧消耗为10.2±0.7 nmol O2·min-1·mg蛋白-1，装载胱氨酸的小管中为11.4±1.0 nmol O2·min-1·mg蛋白-1。因此，近端小管细胞内胱氨酸装载特异性抑制了针对转运的氧代谢。与对照近端小管相比，当用制霉菌素使细胞对钠通透以及线粒体呼吸解偶联时，装载胱氨酸的近端小管的氧消耗率也较低。甘氨酸是一种对缺氧近端小管损伤具有细胞保护作用的氨基酸，可改善在装载胱氨酸的小管中观察到的呼吸功能障碍。
